A three-dimensional culture system recapitulates placental syncytiotrophoblast development and microbial resistance.

Journal Article (Journal Article)

In eutherians, the placenta acts as a barrier and conduit at the maternal-fetal interface. Syncytiotrophoblasts, the multinucleated cells that cover the placental villous tree surfaces of the human placenta, are directly bathed in maternal blood and are formed by the fusion of progenitor cytotrophoblasts that underlie them. Despite their crucial role in fetal protection, many of the events that govern trophoblast fusion and protection from microbial infection are unknown. We describe a three-dimensional (3D)-based culture model using human JEG-3 trophoblast cells that develop syncytiotrophoblast phenotypes when cocultured with human microvascular endothelial cells. JEG-3 cells cultured in this system exhibit enhanced fusogenic activity and morphological and secretory activities strikingly similar to those of primary human syncytiotrophoblasts. RNASeq analyses extend the observed functional similarities to the transcriptome, where we observed significant overlap between syncytiotrophoblast-specific genes and 3D JEG-3 cultures. Furthermore, JEG-3 cells cultured in 3D are resistant to infection by viruses and Toxoplasma gondii, which mimics the high resistance of syncytiotrophoblasts to microbial infections in vivo. Given that this system is genetically manipulatable, it provides a new platform to dissect the mechanisms involved in syncytiotrophoblast development and microbial resistance.

Full Text

Duke Authors

Cited Authors

  • McConkey, CA; Delorme-Axford, E; Nickerson, CA; Kim, KS; Sadovsky, Y; Boyle, JP; Coyne, CB

Published Date

  • March 2016

Published In

Volume / Issue

  • 2 / 3

Start / End Page

  • e1501462 -

PubMed ID

  • 26973875

Pubmed Central ID

  • PMC4783126

International Standard Serial Number (ISSN)

  • 2375-2548

Digital Object Identifier (DOI)

  • 10.1126/sciadv.1501462

Language

  • eng

Conference Location

  • United States